Cannabinoid receptors belong to G-protein conjugated receptor having the seven transmembraneous domain. Among these, CB1 receptor is predominately distributed in the central nervous system, of which existence is known by Devane W A et al. (Molecular Pharmacology, 34, 605-613 (1988)). CB2 receptor, which has a predominant cell distribution in the immune system and in the peripheral tissues, has been discovered by Munro S et al. (Nature, 365, 61-65 (1993)). CB1 receptor and CB2 receptor show 48% of homology. 97-99% amino acid sequence of CB1 receptor is maintained in rat, mouse and human.
In the brain, CB1 receptor exists predominately in hippocampus, striatum, substanta nigra, basal forebrain area, olfactory bulb and cerebellum, and little in the brain stem, medulla and thalamus. CB1 receptor is localized in the presynapse, and is considered to control inhibitively the release of neurotransmitters (Trends Pharmacological Sciences, 22, 565-572 (2001)). For CB1 receptor, four kinds of agonist are well known, i.e., classic cannabinoids of tetrahydrocannabinol (THC) derivatives which are dibenzopyran rings, non-classic cannabinoids which are bicyclic and tricyclic derivatives prepared by cleavage of the pyran rings of the THC structure, aminoalkyl indols, and arachidonic acid derivatives such as anandamide which is known as an endogenous agonist (Science, 258, 1946-1949 (1992)).
WIN55,212-2, a cannabinoid receptor agonist, has been reported to inhibit neural cell death based on cerebral ischemia (Journal of Neuroscience, 19, 2987-2995 (1999)). The action is believed to be caused by inhibiting the release of glutamic acid through the activation of the CB1 receptor in the presynapse of glutamic acid neuron. Further, anandamide which is an endogenous ligand has been reported to show inhibitory action on neural cell death after brain injury (Nature, 413, 527-531 (2001)). Further, Baker et al. have reported that WIN55,212-2, JWH-133, THC and methanandamide, which are cannabinoid receptor agonists, improved tremor or spasticity in the animal model of multiple sclerosis (Nature, 404, 84 (2000)).
Cerebrovascular disorders are the 2nd or 3rd leading cause of death in Japan, USA and Europe, and the 1st leading cause of serious aftereffect of diseases, incurring a big medical loss. At present, active treatment to resolve the etiology (tPA, etc.) is performed for some of the patients suffering from cerebro-embolism and cerebro-thrombus, but it can be applied only to several percentages of the patients due to limited time-window for treatment. In most cases, only maintenance therapy of inhibiting cerebral edema and suppressing recurrence or enlargement (thrombolytics) has been performed, but effective drugs for treating the etiology or protecting the brain have not been developed. So far, many drugs having various mechanisms (e.g., glutamate antagonist, calcium antagonist, antioxidant, etc.) have been tried, but most of them have failed in the clinical trials.
Clinical efficacy of the brain-hypothermia therapy as a brain protecting therapy, has been studied, with building up intensive care system for cerebral stroke. Brain-hypothermia therapy is a therapy that maintains the brain temperature (cerebral temperature) low as 32 to 33° C., which has prominent brain-protecting effects. Therefore, this therapy has been drawing attention. However, this therapy requires 24-hour intensive care by intensive treatment facility and many staffs, which makes it difficult to be accepted as a general therapy.
On the other hand, the following compounds have been reported as a compound which has an aminoacyl group on the benzene ring of a bicyclic heterocycle in which the benzene is fused with a 5-membered heterocycle.
1) A compound represented by the following Formula

[wherein, R3 is an acylamino group, etc.] (Pamphlet of WO02/085866) which has analgesic action.
2) A compound represented by the following Formula

[wherein, W is an acylamino group, etc.] which has proliferating and differentiating action on stem cells or precursor cells of neuron (JP-A-2002-348239).
3) A compound represented by the following Formula
[wherein, the group NR1R2 is an amincacyl group, etc.] which has sodium channel regulating action (Pamphlet of WO98/08842).